Various inhibitors (sterols, bile acids) of cholesterol synthesis in cultured human skin fibroblasts cause within 10-30 minutes phosphorylation of HMGCoA reductase and a concomitant depression of its expressed activity with the total activity remaining unchanged. Longer periods of incubation of fibroblasts with these inhibitors reduce progressively the total activity of the enzyme. Active HMGCoA reductase kinase is required for the phosphorylating action and the kinase is active only in its phosphorylated form.